Studies Of Distribution And Metabolism Of Ketamine In Hair Of Guinea Pigs

Objective Studies of distribution and metabolism of ketamine in hair of guinea pigs and effects of administration route , form, dose and hair color on it.Methods 1. Analysis method: The specimen of hair were added in internal standard object(SKF_525A) after cleaned and hydrolyzed, and then were alkalified and extracted with ethyl acetate. The extracts were qualitated by GC/MS full scan method and quantitated by internal standard and working curve methods.2. Distribution and metabolism study: Models of guinea pigs administrated a single dose or continuous doses of hydrochloride of ketamine were established. The experimental group were given hydrochloride of ketamine through i.g administration or i.p injection. The hair samples were collected at different time points after drug administration. Guinea pigs in control group were given physiologic saline through i.g administration or i.p injection. The hair samples were collected as blank control. The distribution and metabolism of ketamine were studied by hair segment analysis. Three group guinea pigs of high, middle, low administrated doses and the other three group guinea pigs of black, brown, white hair were engineered to study the influence of administrated dose and hair color to the distribution and metabolism of ketamine in hair.Results 1. The linear range for ketamine and norketamine in hair of guinea pigs by GC/MS was 0.1～100ng·mg^-1.The limit of detection was 0.06ng·mg^-1 and analytical recovery was 92.36%～105.85%. The inter- and intra-day relative standard deviations of precisions were less than 10 % and 15% respectively.2. Ketamine and norketamine could be detected in hair of guinea pigs after administrated hydrochloride of ketamine. The concentration of ketamine and norketamine was highest at the third day after administrated drug with a single dose, and that could not be detected in the tenth day. In hair of guinea pigs which were administrated drug with continuous doses, the concentration of ketamine and norketamine was highest at the third day after the last administration. Ketamine and norketamine could still be detected at the 20th day. There was no significant difference be shown in the concentration of ketamine and norketamine between the i.g administration group and i.p injection group(P>0.05).3. The concentration of ketamine and norketamine in hair samples was changed with the administrated doses(P<0.05), which have significant correlation. The correlation coefficient(r) was 0.91 and 0.84 respectively.4. The concentration of ketamine and norketamine was different with hair color of guinea pigs (P<0.05). The sequence of concentration in hair samples was as follow: black hair >brown hair >white hair.Conclusion 1. The GC and GC/MS methods for the simultaneous determination of ketamine and its metabolite norketamine in hair of guinea pigs were established. The method was proved to be simple, sensitive and reproducible and could be applied to analyse in toxication and abuse cases of ketamine.2. Ketamine and its metabolite could enter into hair of guinea pigs after abused, and could be detected in a long time. Ketamine and norketamine could accumulate in hair of guinea pigs after administrated drug with continuous doses, so it can be detected in a longer time compared with that in hair of guinea pigs which administrated drug with a single dose. It indicate that hair analysis method can be used in ketamine abused case .3. The drug concentration in hair and administrated doses had significant correlation. Abused information can be inferred from hair analysis in practical application.4. Hair color could affect the distribution of ketamine in hair of guinea pigs. The influence of hair color to analysis results shoud be considered in practical application.